Measuring the molecular mechanisms linking diet and prostate cancer

Dr. Alan Kristal's research, using DNA-microarray technology to study the effect of diet on prostate tissue, may provide insights into the molecular mechanisms underlying the association of diet and obesity on prostate-cancer progression.

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While there is good evidence from population-based, observational studies that obesity and a high-fat diet are associated with a greater risk of high-grade, aggressive prostate cancer and prostate-cancer death, the molecular mechanisms underlying these associations have remained largely unknown. The reason: It has been difficult to test the effect of diet on prostate tissue because such tissue has been largely unavailable for study. Human studies of the dietary effects on prostate-cancer risk and progression have generally been limited to measuring circulating biomarkers, such as steroid hormones, in the blood.

In the first randomized clinical trial of its kind — a pilot study involving eight men newly diagnosed with localized prostate cancer — researchers at the Hutchinson Center and the University of Washington School of Medicine have shown that DNA-microarray technology can effectively measure the impact of a low-fat, low-glycemic (low carbohydrate) diet on gene expression in prostate tissue.

Six-week diet modification

The senior author of the paper, described in the October issue of Cancer Epidemiology, Biomarkers and Prevention, is Dr. Alan Kristal, of the Public Health Sciences Division. The lead/corresponding author is Dr. Daniel Lin, of the PHS Division and UW department of urology. They compared baseline gene expression from tissue obtained at the time of biopsy to gene activity in the prostate at the time of prostate removal (the tissue was sampled prior to cutting off the prostate blood supply).

During the six weeks between biopsy/diagnosis and prostatectomy, half of the men received random assignment to follow a low-fat, low-carbohydrate diet and half received assignment to continue their usual dietary habits. The researchers found that just six weeks of sticking to the low-fat, low-carb regimen produced significant gene-expression changes in the prostate tissue. In particular, the dietary intervention had a significant impact on genes that control response to oxidative damage and cell growth, both of which can contribute to cancer development.

Benefits of new approach

Kristal and Lin's research suggests that using this approach to study the effect of diet on prostate tissue may provide new insights into the molecular mechanisms underlying the association of diet and obesity on prostate-cancer progression. Support for the research came from the Center and the National Cancer Institute.